Cardiac beta-adrenoceptor sensitivity and Parkinson's disease.

Certain clinical manifestations of Parkinson's disease (PD) (speech or/and balance disturbances) are not linked to brain dopamine deficiency. The purpose of the present study was to search for a possible relationship between those so-called "non-dopamine-dependent" extrapyramidal manifestations and the sensitivity of cardiac beta-adrenoceptors. Fourteen patients aged 51 to 69 were included in the study after having given their informed consent. Any factor or pathology susceptible to modify receptor sensitivity entailed exclusion. In the absence of a reference model for measuring the reactivity of central beta-adrenoceptors, a computation of the isoprenalin dose necessary to increase the resting heart rate by 20 bpm was used as an index for beta-adrenergic system reactivity. In addition to that test, other parameters were recorded: disease duration, motor status scale (Columbia), some cognitive functions (MMS and image differed recall). The cardiac beta-receptor decrease in reactivity to isoproterenol is correlated to PD duration (r = 0.8, P less than 0.001). Conversely, the sensitivity of these receptors appeared to be unrelated to the extrapyramidal severity of the disease, hence to the degree of the so-called "non dopamine-dependent" disturbances. Furthermore, such results raise the meaning of the impairment of peripheral aminergic receptors in the cognitive disturbances linked to ageing and/or PD.

Randomized double-blind trial of injectable heptaminol for controlling spontaneous or bromocriptine-induced orthostatic hypotension in parkinsonians.

Heptaminol is a molecule with experimental cardiovascular analeptic properties. In this double-blind vs placebo trial, the potency, so far unproven, of the injectable form of a 626 mg dose of heptaminol chlorhydrate on spontaneous or induced orthostatic hypotension (OH), was assessed. Nineteen patients were included in the study: 7 displayed spontaneous OH, and in the other 12 OH was induced by bromocriptine, as monitored 103 min/after an oral intake of 6.6 mg on average. Neither spontaneous nor induced OH were recorded in 32% of the Parkinsonian population registered, with no obvious distinctive characteristics. Potency tilt-trials, performed 15, 30 and 45 min after parenteral administration of heptaminol, revealed a significant and expressive potency of the molecule on the systolic blood pressure after 15 min (P less than 0.05). Clinical and biological tolerance was excellent. Low plasma renin activity and the absence of response to orthostatism indicated, in this population of Parkinsonian extrapyramidal syndromes, a loss in positive tonus likely to be of sympathetic origin. The anti-hypotensive action of heptaminol does not seem to be related to any renal or even sympathetic interaction.

Randomized, double-blind trial of exifone versus cognitive problems in Parkinson's disease.

Exifone is a novel substance of the benzophenone group that possesses potent scavenging properties. Initial findings demonstrate beneficial effects on age-related cognitive disorders. In this double-blind clinical trial versus placebo, the efficacy of 2 dosages (600 and 1200 mg/d) was evaluated with regard to Parkinson's disease (PD)-related cognitive disorders, for which there is increasing suspicion of a free-radicals origin. Despite disparities between the treatment groups as assessed by validated scales and subtests, and a considerable placebo effect on main parameters, both dose levels of exifone produced statistically significant improvement of the cognitive items most commonly impaired by PD: immediate recall, naming of objects presented, spatiotemporal orientation, and calculation. These properties suggest a new slot for exifone in the range of therapeutics available.

Rupture of the uterus during labor without apparent cause.

Spontaneous uterine rupture at term during labor of a non-scarred uterus under epidural anaesthesia is reported in a 17-yr-old primigravida. This exceptional event may lead to catastrophic maternal and fetal consequences. The authors discuss the prevention and diagnosis of this obstetrical complication.

Erythromycin lactobionate: pharmacokinetics and uterine tissue levels.

Erythromycin is well-known for its properties of tissular diffusion. An estimation of its concentration in uterine tissue seemed worthwhile, in order to justify the use of erythromycin lactobionate in uterine infections by sensitive micro-organisms. The authors studied the uterine levels of this macrolid, after perfusion of 1g of erythromycin lactobionate, over a period of one hour. The protocol involved a group of 15 women, who were to undergo a hysterectomy for benign non-inflammatory pathology. The uterine specimens and plasmatic pharmacokinetics of the antibiotic constitute the data. The concentrations of antibiotic were determined by microbiological methods. 2 sets of results emerge: during perfusion, the uterine erythromycin levels are equal or inferior to simultaneous serum levels. after perfusion, the uterine levels are superior to serum levels. A bicompartmental linear model was used, which simulated the tissular levels in standard treatment with erythromycin lactobionate. If the erythromycin 4 micrograms/ml critical concentration is compared with uterine tissue concentration, the antibiotic may be expected to be active against a uterine affected by sensitive micro-organisms during a period of approximately 5 hours. This result must be confirmed by a clinical study.

[Torsade de pointes. Apropos of 54 cases]. / Les torsades de pointe. A propos de 54 cas.

A retrospective study of 54 torsades de pointe cases in a cardiology department enabled us to specify the main characteristics of this serious arrythmia often observed in intensive care units: --the diagnostic criteria: more than the pattern of tachycardia attack, late ventricular premature beats and particularly QT prolongation are necessary for proper diagnosis. These two criteria allow us to differentiate between torsades de pointe and multiform ventricular tachycardia with similar morphology especially in acute myocardial ischaemia; --their clinical repercussion: the shortness of circulatory arrest related to the spontaneous end of the arrythmia explains that the torsades de pointe often result in short faintings. Nevertheless, they may degenerate into ventricular fibrillation (17 p. 100) which, in cases of recurrence, induced four deaths in this study; --there are many possible aetiologies often associated (30 p. 100) in the same patient. Their research must be exhaustive in each case. The chronic bradycardias especially the atrioventricular blocks of two or three degree whether continuous or not are often responsible (57 p. 100). Then, the metabolic disorders, essentially hypokalaemia and constant drug administration (antiarrythmic agents belonging to group I of Vaughan William's classification, some antianginal drugs, vasodilatator drugs) are often chief causative agents. Other aetiologies are rare. In 9 p. 100 of cases, no aetiological factor is found; --the best treatment is to suppress aetiological factors, to stop the administration of antiarrhythmic drugs; torsades de pointe must be controlled by increasing the heart rate; pace maker stimulation is the best way of making QT shorter and thus of synchronizing ventricular depolarization.

[Epidural anesthesia during labor: comparison of 3 combinations of fentanyl-bupivacaine and bupivacaine alone]. / Analgésie péridurale au cours du travail: comparaison de trois associations fentanyl-bupivacaïne et de la bupivacaïne seule.

The association of bupivacaine and fentanyl appeared as the best method of inducing satisfactory obstetrical analgesia. But the various techniques of drug administration had to be detailed; this justified the present work, a single-blind controlled trial performed on 159 primipara women at term (except one of them), randomized in four groups, after informed consent. In each group, the number of patients, the age and the degree of uterine dilatation at the beginning of the epidural anaesthesia were comparable. Epidural anaesthesia aimed to improve the maternal comfort during labour. After a first epidural injection of 10 ml, several other injections of 6 ml were carried out according to four different protocols (I, II, III, IV), with different concentrations of fentanyl (respectively 0, 0.05, 0.1 and 0.15 mg). The mean total dosages of fentanyl were statistically higher in the protocols III and IV. The foetal cardiac rhythm and uterine contractions were monitored continuously as well as maternal blood pressure and heart beats during labour. The following parameters were assessed: contraction pain intensity (five point scale), the onset of analgesia, the duration of analgesia, the length of labour, the interval between the first drug injection and subsequent injections, the type of delivery. In the newborn, Apgar score was assessed at 1, 5 and 10 min after delivery. The degree of analgesia was statistically improved in the groups receiving fentanyl, without any differences between them. On the other hand, the length of labour was shorter with protocol II (lowest concentration of fentanyl).(ABSTRACT TRUNCATED AT 250 WORDS)

[Cerebral edema: intra-cellular or extra-cellular mechanisms?]. / L'oedème cérébral: mécanisme intra-cellulaire ou extra-cellulaire?

Many cerebral pathological processes are attended by edema defined as an increase in brain volume associated with an increase in brain water and sodium contents. The aggravation of lesions induced by this edema warrants a pharmacological and therapeutic approach based on a detailed knowledge of its physiopathological mechanisms. Experimental models and in vitro studies have shown that the fundamental mechanisms leading to edema are: cold, acute hypoxia, ischaemia, arachidonic acid, toxic substances and plasma hypo-osmolarity. To the various types of edema described (vasogenic, cytotoxic, hydrocephalic) correspond different mechanisms. Vasogenic edema essentially depends on osmotic and hydrodynamic factors; cytotoxic edema results from perturbations in energy-dependent cellular osmoregulation. The underlying biochemical disorders have now been demonstrated, mostly in ischaemic edema; they include, during the revascularization phase, disruption of the blood-brain barrier (vasogenic component) and changes in ion concentrations, neurotransmitters and energetic mechanisms. Key factors in the development of edema are cyclic AMP, serotonin and Na-K-ATPase.

[Epidural anesthesia using the bupivacaine-fentanyl combination for cesarean section]. / Anesthésie péridurale pour césarienne par association bupivacaïne-fentanyl.

This prospective study was designed to evaluate the benefit of a bupivacaine-fentanyl mixture vs bupivacaine alone in epidural anaesthesia for caesarean section. In 10 women, 0.5% bupivacaine (1.18 ml per metamer) was injected in the epidural space. In 20 women, 0.5% bupivacaine (1.06 ml per metamer) was injected by the same route together with fentanyl (1.70 +/- 0.09 micrograms X kg-1). The bupivacaine-fentanyl group showed a significantly shortened onset of analgesia (p less than 0.001), as well as a significant reinforcement of this analgesia graduated from 0 to 4 (p less than 0.01 at 25 min, p less than 0.001 at 75 min and at the maximum of pain, for the two sets of scores). All the Apgar scores were maximal at 5 min. No clinical respiratory depression was observed in either the mothers or the neonates. Fetal and maternal blood concentrations were in favour of respiratory innocuousness of the method (peak fentanyl concentrations: in mothers 1.5 ng X ml-1, in neonates 0.8 ng X ml-1). Fentanyl never induced any significant haemodynamic variations. Pruritus and nausea respectively occurred in six and two patients respectively in the bupivacaine-fentanyl group. In conclusion, in caesarean section, the adjunction of fentanyl to bupivacaine significantly improved analgesia without any clinical respiratory depression both in the mother and the neonate.

[Radical prostatectomy and biologic glue]. / Prostatectomie radicale et colle biologique.

Fibrin glue (reconstituted fibrin glue-Tissu-col-Immuno-France) was used in 24 patients following radical prostatectomy with ilio-obturator lymphadenectomy (Group II) to improve haemostasis of the operative field, to decrease or eliminate lymphatic oozing and to promote healing of the urethrovesical anastomosis. The results in terms of duration of drainage, quantity of fluid evacuated by these drains, operative complications and length of hospital stay were compared to those obtained in 24 clinically identical patients operated previously without the use of fibrin glue (Group I). Although fibrin glue is easy to use, ensures a particularly dry operative field at the end of the operation and does not induce any infectious complications (abscess, hepatitis), it increases the cost of the operation (5 ml vial = 2,500 FF) and the use of this product does not reduce the drainage time (Group I: 7 +/- 4.6 days; Group II: 8.5 +/- 5.4 days) the volume of blood or lymphatic discharge (Group I: 500 +/- 570 ml; Group II: 660 +/- 825 ml) or the length of hospital stay (Group I: 16.5 +/- 4.8 days; Group II: 17.4 +/- 5.5 days). These results argue against the routine use of fibrin glue in radical prostatectomy.

[Acquired experience in anesthesia and perioperative intensive care in percutaneous nephrolithotomy. Current approach in the endoscopic treatment of lithiasis and pyelo-ureteral junction anomalies]. / Expérience acquise en anesthésie et réanimation péri-opératoire dans la néphrolithotomie percutanée. Attitude actuelle dans le traitement endoscopique de la lithiase et de l'anomalie de la jonction pyélo-urétérale.

Percutaneous endoscopic treatment of the kidney retains a place in the treatment of renal stones (percutaneous nephrolithotomy--PCNL) and ureteropelvic junction abnormalities (endopyeloplasty). It requires anaesthesia ensuring surgical comfort and safety for the patients despite changes in position and the prolonged ventral supine position. The operation carries certain iatrogenic risks related to caliceal irrigation in patients with more or less documented episodes of infection and carries risks of haemorrhage and effraction of adjacent organs. 282 patients treated by PCNL between 1984 and 1991 were reviewed in order to define the respective indications for general anaesthesia and peridural anaesthesia and to determine the modalities, to evaluate the risk and severity of absorption of irrigation fluid and to assess the risk of infection by defining the indications for prophylactic antibiotics. General anaesthesia, using etomidate and propofol via an infusion pump, ensures surgical comfort, anaesthetic safety and better control of intraoperative complications. The renewed interest in this technique must be counterbalanced by the growing incidence of anaphylactic reactions related to anaesthetic drugs. Operations lasting more than 2 hours, raised intracaliceal pressure, the initially exclusive use of glycine for irrigation induce haemodilution complications, possibly aggravated by glycine intoxication. Repeated surgery is preferable with the use of an Amplatz tube as often as possible and physiological saline, except when required by the operation. Patients with a history of urinary tract infection or infected stones should receive prolonged and effective antibiotics before, during and after the operation. Prophylactic antibiotics are reserved for those patients with no history of infection. These principles equally apply to percutaneous nephrolithotomy and endopyeloplasty.

[Morphine in cesarean section and postoperative analgesia]. / Les morphiniques dans les césariennes et en analgésie postopératoire.

Epidural opioids for caesarean section are routinely used by many anaesthesists. Combined epidural injection of a local anaesthetic and an opioid provides a more rapid onset of profound analgesia. No side effects are observed in either the mother or the neonate with epidural "microdoses" of sufentanil or fentanyl, but the postoperative analgesia is of short duration. Combined intrathecal injection on 0.1-0.2 mg morphine and 0.5% hyperbaric bupivacaine provides a better intra- and postoperative analgesia. Opiates used during anaesthesia in toxemic women before delivery imply strict subsequent paediatric care. Good postoperative analgesia can be obtained with intrathecal morphine or patient-controlled analgesia. Using other techniques depends on care and surveillance facilities. Opiates by spinal or intravenous route are not dangerous for breast-fed newborns.

[Neuroleptanalgesia for chemical nucleolysis]. / Neuroleptanalgésie pour la nucléolyse chimique.

38 cases of chemionucleolysis, under neuroleptanalgesia by droperidol-Fentanyl with spontaneous respiration are reported. This technique was satisfactory and allowed the patient to cooperate.